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<p>While Roux-en-Y gastric bypass is an effective treatment for obesity and type 2 diabetes, up to one-third of patients develop post-bariatric hypoglycaemia (PBH). Individuals with PBH exhibit increased postprandial secretion of the intestinal hormone fibroblast growth factor 19 (FGF19, Fgf15 in mice). However, the underlying mechanisms contributing to PBH remain uncertain. Here we demonstrate that faecal and plasma bile acid (BA) profiles are significantly altered in postoperative individuals with PBH versus those without hypoglycaemia. Furthermore, altered BAs in PBH induce FGF19 secretion in intestinal cells in a manner dependent on the apical sodium-dependent BA transporter (ASBT). We demonstrate that ASBT inhibition reduces Fgf15 expression and increases postprandial glucose in hypoglycaemic mice. Our data suggest that dysregulation of luminal BA profiles and transport may contribute to PBH and provide proof of concept that ASBT inhibition could be developed as a new therapeutic strategy for PBH.</p>

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Alterations in intestinal bile acid transport provide a therapeutic target in patients with post-bariatric hypoglycaemia

  • 期刊论文

  • 发表日期：

    2025年4月4日

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  • Snehal N. Chaudhari,
  • Yingjia Chen,
  • Rafael Ferraz-Bannitz,
  • Cameron Cummings,
  • Amanda Sheehan,
  • Pilar Casanova Querol,
  • Berkcan Ozturk,
  • Hanna Wang,
  • Gabriel D’Agostino,
  • Fei Ye,
  • Eric G. Sheu,
  • A. Sloan Devlin,
  • Mary-Elizabeth Patti

摘要

While Roux-en-Y gastric bypass is an effective treatment for obesity and type 2 diabetes, up to one-third of patients develop post-bariatric hypoglycaemia (PBH). Individuals with PBH exhibit increased postprandial secretion of the intestinal hormone fibroblast growth factor 19 (FGF19, Fgf15 in mice). However, the underlying mechanisms contributing to PBH remain uncertain. Here we demonstrate that faecal and plasma bile acid (BA) profiles are significantly altered in postoperative individuals with PBH versus those without hypoglycaemia. Furthermore, altered BAs in PBH induce FGF19 secretion in intestinal cells in a manner dependent on the apical sodium-dependent BA transporter (ASBT). We demonstrate that ASBT inhibition reduces Fgf15 expression and increases postprandial glucose in hypoglycaemic mice. Our data suggest that dysregulation of luminal BA profiles and transport may contribute to PBH and provide proof of concept that ASBT inhibition could be developed as a new therapeutic strategy for PBH.